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Asymmetric dimethylarginine positively modulates calcium-sensing receptor signalling to promote lipid accumulation.
- Source :
-
Cellular Signalling . Jul2023, Vol. 107, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- Asymmetric dimethylarginine (ADMA) is generated through the irreversible methylation of arginine residues. It is an independent risk factor for cardiovascular disease, currently thought to be due to its ability to act as a competitive inhibitor of the nitric oxide (NO) synthase enzymes. Plasma ADMA concentrations increase with obesity and fall following weight loss; however, it is unknown whether they play an active role in adipose pathology. Here, we demonstrate that ADMA drives lipid accumulation through a newly identified NO-independent pathway via the amino-acid sensitive calcium-sensing receptor (CaSR). ADMA treatment of 3T3-L1 and HepG2 cells upregulates a suite of lipogenic genes with an associated increase in triglyceride content. Pharmacological activation of CaSR mimics ADMA while negative modulation of CaSR inhibits ADMA driven lipid accumulation. Further investigation using CaSR overexpressing HEK293 cells demonstrated that ADMA potentiates CaSR signalling via G q intracellular Ca2+ mobilisation. This study identifies a signalling mechanism for ADMA as an endogenous ligand of the G protein-coupled receptor CaSR that potentially contributes to the impact of ADMA in cardiometabolic disease. • Asymmetric dimethylarginine promotes lipogenesis in adipocytes and hepatocytes. • Lipid accumulation is independent of nitric oxide blockade. • Asymmetric dimethylarginine can modulate Calcium-sensing receptor signalling. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08986568
- Volume :
- 107
- Database :
- Academic Search Index
- Journal :
- Cellular Signalling
- Publication Type :
- Academic Journal
- Accession number :
- 163587464
- Full Text :
- https://doi.org/10.1016/j.cellsig.2023.110676